Eosinophilia and Symptomatic Pulmonary Amyloidosis a a Haydar, a Li, R Hilton, B Lams, R Hangartner, M Weber, D J a Goldsmith

738 Postgrad Med J: first published as 10.1136/pgmj.2003.013052 on 3 December 2004. Downloaded from CASE REPORT Eosinophilia and symptomatic pulmonary amyloidosis A A Haydar, A Li, R Hilton, B Lams, R Hangartner, M Weber, D J A Goldsmith ......

Postgrad Med J 2004;80:738–739. doi: 10.1136/pgmj.2003.013052

weeks later, the patient was readmitted with a significant The case of a man with progressive breathlessness and respiratory deterioration. There was no peripheral eosinophi- pulmonary infiltration caused by AL amyloidosis associated lia. High resolution computed tomography of the chest with multiple myeloma is presented. There was a marked demonstrated calcified pleural plaques, irregular consolida- peripheral eosinophilia, which has not previously been tion in the right lower lobe, and widespread ground glass described with amyloidosis. opacification (see fig 1). Bronchoscopy was normal and polymorphonuclear leucocytes were seen on bronchoalveolar lavage; there was no evidence of infectious organisms. Attempted transbronchial biopsy (no lung parenchyma) osinophilia is a challenging disease with a wide showed normal bronchial mucosa. Open lung biopsy revealed differential diagnosis (see box 1). A broad variety of widespread homogenous deposits in alveolar walls, bronch- Eallergic, infectious, neoplastic, and idiopathic diseases ioles and pulmonary vessels, confirmed as amyloidosis by are associated with increased blood and/or tissue eosinophilia Congo red staining. The patient became progressively more and range in severity from self limited conditions to life breathless and died shortly after. threatening disorders. We report a patient who had marked peripheral eosinophilia associated with pulmonary symp- DISCUSSION toms. He was diagnosed to have pulmonary amyloidosis. The patient presented with peripheral eosinophilia and pulmonary amyloidosis. The cause of the peripheral CASE REPORT A 72 year old man presented with a serum creatinine concentration of 300 mmol/l, haemoglobin 97 g/l, and hyper- Box 1: Eosinophil associated diseases and calcaemia. Renal ultrasound revealed two small kidneys with disorders thin cortices; 24 hour urine protein was 3.4 g. A kidney biopsy specimen showed focal scarring of the interstitium Allergic diseases only, and some fractured renal tubular casts. Congo red N Atopic and related diseases. staining was negative. Urine immunoelectrophoresis showed N Medication related eosinophilia. free lambda light chains with a low plasma immunoglobulin level. Bone marrow trephine biopsy confirmed the presence Infectious diseases http://pmj.bmj.com/ of 25% plasmacytosis consistent with multiple myeloma. N Parasitic infections mostly with helminths. Chemotherapy was started with cyclophosphamide, dex- N amethasone, and pamidronate. Progression to end stage renal Special fungal infection. failure was rapid, necessitating continuous ambulatory Haematological and neoplastic disorders peritoneal dialysis and cessation of chemotherapy. N Hypereosinophilic syndrome. Two years later, the patient was admitted with a month’s N history of progressive dyspnoea. Examination revealed N Leukaemia. bibasilar crackles and a friction rub. Chest radiography Lymphoma. on September 29, 2021 by guest. Protected copyright. showed bilateral lower zone infiltrates and arterial blood N Tumour associated. gases on room oxygen demonstrated a partial pressure of N Mastocytosis. oxygen of 7.6 kPa and partial pressure of carbon dioxide of 5.5 kPa. The white cell count was 10 6 109/l with an Diseases with specific organ involvement eosinophilia of 35% (normal previously); the absolute N Skin and subcutaneous diseases. eosinophil count was 3500 cell/ml. High resolution computed N Pulmonary diseases. tomography of the chest showed ground glass opacities in both lungs with confluent nodules on the right. Pulmonary N Gastrointestinal diseases. function tests demonstrated a restrictive pattern (forced N Neurological diseases. expiratory volume in one second = 1.18 l, forced vital N Rheumatological diseases. capacity = 1.33 l) and impaired gas exchange. Bronchoscopy N Cardiac diseases. showed normal mucosa. Cytology revealed eosinophils. There N Renal diseases. was no evidence of fungi, mycobacterium, parasites, cyto- megalovirus, or Pneumocystis carinii pneumonia. Autoantibody Immunological reactions screen and complement (C3, C4) were all normal and N Specific immune deficiencies. strongyloides ELISA antibodies negative. The working diagnosis was acute eosinophilic pneumonia N Transplant rejection. and 60 mg daily oral prednisolone was started and continued Endocrine (at variable doses) until his death eight month’s later. Peripheral eosinophilia resolved completely after a few days, N Hypoadrenalism. but the patient’s dyspnoea improved only marginally. A few

www.postgradmedj.com Pulmonary amyloidosis 739 Postgrad Med J: first published as 10.1136/pgmj.2003.013052 on 3 December 2004. Downloaded from

Learning points

N Differential diagnosis of peripheral eosinophilia. N To learn more about pulmonary amyloidosis: aetiol- ogy, different types, radiological appearance, treat- ment, and prognosis.

An association of eosinophilia and amyloidosis has not previously been reported. By the time a diagnostic lung biopsy was obtained the patient had been on oral steroids for some months, and the peripheral eosinophilia had resolved; no eosinophilic lung infiltration was noted on Figure 1 High resolution computed tomogram of the chest showing the lung biopsy, which was remarkable for extensive ground glass opacities in both lungs with confluent nodules on the right. amyloidosis. The only therapy that might have been effective for the patient is chemotherapy for primary amyloidosis (for eosinophilia was investigated thoroughly. History and phy- example, melphalan and prednisone). Patients who have a sical examination ruled out most of the differential diagnoses chemotherapeutic response may have an extended survival.3 listed in box 1 (transplant rejection, rheumatological and However no controlled trials comparing different chemother- gastrointestinal diseases). The patient was given a course of apeutic regimens in pulmonary amyloidosis are available. The steroids and his eosinophilia disappeared but not his chest patient’s condition deteriorated quickly and in view of his symptoms. frailty it was felt he would not withstand chemotherapy. Pulmonary amyloidosis was diagnosed as the cause of the patient’s progressive lung disease, and was confirmed with ...... Congo red staining on tissue biopsy. Amyloidosis, whether Authors’ affiliations disseminated or localised in the lung, has not been reported A A Haydar, A Li, R Hilton, D J A Goldsmith, Renal and Transplantation before as associated with peripheral eosinophilia. Amyloi- Unit, Guy’s and St Thomas’ Hospitals, London, UK dosis is known to affect virtually any organ system except for B Lams, Chest Medicine, Guy’s and St Thomas’ Hospitals, London, UK the brain. In postmortem studies of amyloid patients, the R Hangartner, M Weber, Histopathology, Guy’s and St Thomas’ lungs can be affected by amyloidosis—usually the primary/ Hospitals, London, UK multiple myeloma (AL), rather than the secondary (AA) type1—but symptomatic pulmonary syndromes are much Correspondence to: Dr David J A Goldsmith, Guy’s Hospital, London SE1 9RT, UK; [email protected] rarer. Pulmonary amyloidosis is usually a silent disease with scanty respiratory signs; most of the patient symptoms are Submitted 25 July 2003 derived from amyloid infiltration of the heart and kidneys. Accepted 29 August 2003 Pulmonary function testing sometimes not always reveals a restrictive pattern.2 Pulmonary involvement is not a major contributor to death REFERENCES http://pmj.bmj.com/ in AL amyloidosis,2 and the median patient survival with 1 Sculz C, Hauck RW, Nathrath WB, et al. Combined amyloidosis of the upper clinically overt lung deposition is about 16 months. The and lower respiratory tract. Respiration 1995;62:163–6. 2 Cordier JF, Loire R, Brune J. Amyloidosis of the lower respiratory tract. disease of our patient was not classical of pulmonary Clinical and pathological features in a series of 21 patients. Chest amyloidosis (asymptomatic and indolent). On the contrary 1986;90:827–31. the patient’s main symptoms were respiratory in nature with 3 Kyle RA, Gertz MA, Greipp PR, et al. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, peripheral eosinophilia and his disease progressed rapidly and melphalan, prednisone, and colchicine. N Engl J Med and he died of respiratory failure. 1997;336:1202. on September 29, 2021 by guest. Protected copyright.